nuclear proteins

Summary

Summary: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.

Top Publications

  1. ncbi DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
    E P Rogakou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 273:5858-68. 1998
  2. ncbi In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Lyubomir T Vassilev
    Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Science 303:844-8. 2004
  3. ncbi Role of histone H3 lysine 27 methylation in Polycomb-group silencing
    Ru Cao
    Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Science 298:1039-43. 2002
  4. ncbi Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis
    Jing Yang
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Cell 117:927-39. 2004
  5. ncbi Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
    Jeremy Schwartzentruber
    McGill University and Genome Quebec Innovation Centre, Montreal, Quebec H3A 1A4, Canada
    Nature 482:226-31. 2012
  6. pmc Selective inhibition of BET bromodomains
    Panagis Filippakopoulos
    Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    Nature 468:1067-73. 2010
  7. pmc RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
    Johannes Zuber
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nature 478:524-8. 2011
  8. pmc Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma
    Ignacio Varela
    Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 469:539-42. 2011
  9. ncbi Mdm2 promotes the rapid degradation of p53
    Y Haupt
    Lautenberg Center for General and Tumor Immunology, The Hebrew University Haddassah Medical School, Jerusalem, Israel
    Nature 387:296-9. 1997
  10. ncbi Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease
    Brinda Ravikumar
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Nat Genet 36:585-95. 2004

Detail Information

Publications266 found, 100 shown here

  1. ncbi DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
    E P Rogakou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 273:5858-68. 1998
    ..Thus, gamma-H2AX formation is a rapid and sensitive cellular response to the presence of DNA double-stranded breaks, a response that may provide insight into higher order chromatin structures...
  2. ncbi In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Lyubomir T Vassilev
    Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Science 303:844-8. 2004
    ..These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice...
  3. ncbi Role of histone H3 lysine 27 methylation in Polycomb-group silencing
    Ru Cao
    Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Science 298:1039-43. 2002
    ..Methylation on H3-K27 facilitates binding of Polycomb (PC), a component of the PRC1 complex, to histone H3 amino-terminal tail. Thus, these studies establish a link between histone methylation and PcG-mediated gene silencing...
  4. ncbi Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis
    Jing Yang
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Cell 117:927-39. 2004
    ..These results establish a mechanistic link between Twist, EMT, and tumor metastasis...
  5. ncbi Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
    Jeremy Schwartzentruber
    McGill University and Genome Quebec Innovation Centre, Montreal, Quebec H3A 1A4, Canada
    Nature 482:226-31. 2012
    ..This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis...
  6. pmc Selective inhibition of BET bromodomains
    Panagis Filippakopoulos
    Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    Nature 468:1067-73. 2010
    ..These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family...
  7. pmc RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
    Johannes Zuber
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nature 478:524-8. 2011
    ....
  8. pmc Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma
    Ignacio Varela
    Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 469:539-42. 2011
    ..4) as a second major ccRCC cancer gene, with truncating mutations in 41% (92/227) of cases. These data further elucidate the somatic genetic architecture of ccRCC and emphasize the marked contribution of aberrant chromatin biology...
  9. ncbi Mdm2 promotes the rapid degradation of p53
    Y Haupt
    Lautenberg Center for General and Tumor Immunology, The Hebrew University Haddassah Medical School, Jerusalem, Israel
    Nature 387:296-9. 1997
    ..During recovery from DNA damage, maximal Mdm2 induction coincides with rapid p53 loss. We propose that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal...
  10. ncbi Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease
    Brinda Ravikumar
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Nat Genet 36:585-95. 2004
    ..Our data provide proof-of-principle for the potential of inducing autophagy to treat Huntington disease...
  11. ncbi WAF1, a potential mediator of p53 tumor suppression
    W S El-Deiry
    Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
    Cell 75:817-25. 1993
    ..These studies define a gene whose expression is directly induced by p53 and that could be an important mediator of p53-dependent tumor growth suppression...
  12. pmc PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues
    Seung Hee Yoo
    Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA
    Proc Natl Acad Sci U S A 101:5339-46. 2004
    ..These results demonstrate that peripheral tissues express self-sustained, rather than damped, circadian oscillations and suggest the existence of organ-specific synchronizers of circadian rhythms at the cell and tissue level...
  13. ncbi Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes
    Jan J Molenaar
    Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    Nature 483:589-93. 2012
    ..The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours...
  14. ncbi The polycomb group protein EZH2 is involved in progression of prostate cancer
    Sooryanarayana Varambally
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nature 419:624-9. 2002
    ..Thus, dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression...
  15. ncbi Regulation of p53 stability by Mdm2
    M H Kubbutat
    ABL Basic Research Program, NCI FCRDC, Frederick, Maryland 21702 1201, USA
    Nature 387:299-303. 1997
    ..Furthermore, mechanisms regulating the Mdm2-induced degradation of p53 may play a role in controlling the extent and duration of the p53 response...
  16. pmc c-Myc regulates transcriptional pause release
    Peter B Rahl
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 141:432-45. 2010
    ..We discuss the implications of these results for the role of c-Myc amplification in human cancer...
  17. ncbi Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
    S M Elbashir
    Department of Cellular Biochemistry, Max-Planck-Institute for Biophysical Chemistry, , Germany
    Nature 411:494-8. 2001
    ..Therefore, 21-nucleotide siRNA duplexes provide a new tool for studying gene function in mammalian cells and may eventually be used as gene-specific therapeutics...
  18. pmc Human CtIP promotes DNA end resection
    Alessandro A Sartori
    The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 450:509-14. 2007
    ..These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination...
  19. ncbi Listening to silence and understanding nonsense: exonic mutations that affect splicing
    Luca Cartegni
    Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
    Nat Rev Genet 3:285-98. 2002
    ..As the splicing mechanisms that depend on exonic signals are elucidated, new therapeutic approaches to treating certain genetic diseases can begin to be explored...
  20. pmc Elucidation of a universal size-control mechanism in Drosophila and mammals
    Jixin Dong
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 130:1120-33. 2007
    ..These results uncover a universal size-control mechanism in metazoan...
  21. ncbi Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK 2100 Copenhagen, Denmark
    Nature 444:633-7. 2006
    ..Thus, senescence in human preneoplastic lesions is a manifestation of oncogene-induced DNA replication stress and, together with apoptosis, provides a barrier to malignant progression...
  22. ncbi The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP
    Jianbin Huang
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
    Cell 122:421-34. 2005
    ..Thus, Yki is a critical target of the Wts/Lats protein kinase and a potential oncogene...
  23. pmc ARID1A mutations in endometriosis-associated ovarian carcinomas
    Kimberly C Wiegand
    British Columbia Cancer Agency, Vancouver, Canada
    N Engl J Med 363:1532-43. 2010
    ..Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described...
  24. pmc Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells
    Yohei Shimono
    Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304, USA
    Cell 138:592-603. 2009
    ..The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells...
  25. pmc AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
    Veit Hornung
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nature 458:514-8. 2009
    ..Collectively, these observations identify AIM2 as a new receptor for cytoplasmic DNA, which forms an inflammasome with the ligand and ASC to activate caspase-1...
  26. pmc Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control
    Bin Zhao
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    Genes Dev 21:2747-61. 2007
    ..Our observations demonstrate that YAP plays a key role in the Hippo pathway to control cell proliferation in response to cell contact...
  27. pmc Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma
    Sian Jones
    Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 330:228-31. 2010
    ..In a total of 42 OCCCs, 7% had mutations in PPP2R1A and 57% had mutations in ARID1A. These results suggest that aberrant chromatin remodeling contributes to the pathogenesis of OCCC...
  28. pmc Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions
    Adrian P Bracken
    Biotech Research and Innovation Centre BRIC, 2100 Copenhagen Ø, Denmark
    Genes Dev 20:1123-36. 2006
    ....
  29. ncbi SWI/SNF nucleosome remodellers and cancer
    BORIS G WILSON
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Division of Hematology Oncology, Children s Hospital Boston, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Nat Rev Cancer 11:481-92. 2011
    ..In this Review we discuss the contributions of SWI/SNF mutations to cancer formation, examine their normal functions and discuss opportunities for novel therapeutic interventions for SWI/SNF-mutant cancers...
  30. ncbi Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice
    L Mangiarini
    Division of Medical and Molecular Genetics, UMDS, Guy s Hospital, London, United Kingdom
    Cell 87:493-506. 1996
    ..This transgenic model will greatly assist in an eventual understanding of the molecular pathology of HD and may open the way to the testing of intervention strategies...
  31. ncbi A microRNA as a translational repressor of APETALA2 in Arabidopsis flower development
    Xuemei Chen
    Waksman Institute, Rutgers University, Piscataway, NJ 08854, USA
    Science 303:2022-5. 2004
    ..Therefore, miRNA172 likely acts in cell-fate specification as a translational repressor of APETALA2 in Arabidopsis flower development...
  32. pmc Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
    Gillian L Dalgliesh
    Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 463:360-3. 2010
    ..These results indicate that substantial genetic heterogeneity exists in a cancer type dominated by mutations in a single gene, and that systematic screens will be key to fully determining the somatic genetic architecture of cancer...
  33. ncbi The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator
    Nicolas Preitner
    Department of Molecular Biology, Sciences II, University of Geneva, 30, Quai Ernest Ansermet, CH 1211 4, Geneva, Switzerland
    Cell 110:251-60. 2002
    ..While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation...
  34. ncbi CRM1 is an export receptor for leucine-rich nuclear export signals
    M Fornerod
    European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 90:1051-60. 1997
    ..We conclude that CRM1 is an export receptor for leucine-rich nuclear export signals and discuss a model for the role of RanGTP in CRM1 function and in nuclear export in general...
  35. pmc A highly efficient recombineering-based method for generating conditional knockout mutations
    Pentao Liu
    Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA
    Genome Res 13:476-84. 2003
    ..This method should also facilitate the generation of knock-in mutations and transgene constructs, as well as expedite the analysis of regulatory elements and functional domains in or near genes...
  36. ncbi The F-box protein TIR1 is an auxin receptor
    Nihal Dharmasiri
    Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
    Nature 435:441-5. 2005
    ..Finally, TIR1 synthesized in insect cells binds Aux/IAA proteins in an auxin-dependent manner. Together, these results indicate that TIR1 is an auxin receptor that mediates Aux/IAA degradation and auxin-regulated transcription...
  37. pmc BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism
    Daniela Boehm
    Gladstone Institute of Virology and Immunology, San Francisco, CA, USA
    Cell Cycle 12:452-62. 2013
    ..Collectively, our results identify BRD2 as a new Tat-independent suppressor of HIV transcription in latently infected cells and underscore the therapeutic potential of BET inhibitors in the reversal of HIV latency...
  38. pmc The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
    Vijay A K Rathinam
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Nat Immunol 11:395-402. 2010
    ..Collectively, our observations demonstrate the importance of AIM2 in the sensing of both bacterial and viral pathogens and in triggering innate immunity...
  39. pmc Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres
    Peter W Lewis
    Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, 1230 York Ave, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:14075-80. 2010
    ..These data demonstrate that Daxx functions as an H3.3-specific chaperone and facilitates the deposition of H3.3 at heterochromatin loci in the context of the ATRX-Daxx complex...
  40. ncbi Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain
    M Difiglia
    Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 277:1990-3. 1997
    ..Ubiquitin was also found in NIIs and DNs, which suggests that abnormal huntingtin is targeted for proteolysis but is resistant to removal. The aggregation of mutant huntingtin may be part of the pathogenic mechanism in HD...
  41. ncbi Molecular mechanisms and potential therapeutical targets in Huntington's disease
    Chiara Zuccato
    Department of Pharmacological Sciences and Centre for Stem Cell Research, Universita degli Studi di Milano, Milan, Italy
    Physiol Rev 90:905-81. 2010
    ....
  42. ncbi Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies
    Rosa Bernardi
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nat Rev Mol Cell Biol 8:1006-16. 2007
    ..Recent data suggest that PML-NBs may be heterogeneous in composition, mobility and function...
  43. ncbi Intrinsically unstructured proteins and their functions
    H Jane Dyson
    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Mol Cell Biol 6:197-208. 2005
    ..Many disordered segments fold on binding to their biological targets (coupled folding and binding), whereas others constitute flexible linkers that have a role in the assembly of macromolecular arrays...
  44. ncbi Role of histone H2A ubiquitination in Polycomb silencing
    Hengbin Wang
    Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Nature 431:873-8. 2004
    ..Thus, our studies identify the H2A ubiquitin ligase, and link H2A ubiquitination to Polycomb silencing...
  45. pmc DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors
    Yuchen Jiao
    Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 331:1199-203. 2011
    ..We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors...
  46. pmc IFI16 is an innate immune sensor for intracellular DNA
    Leonie Unterholzner
    School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
    Nat Immunol 11:997-1004. 2010
    ..IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-β induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs)...
  47. ncbi NeuN, a neuronal specific nuclear protein in vertebrates
    R J Mullen
    Department of Anatomy, University of Utah School of Medicine, Salt Lake City 84132
    Development 116:201-11. 1992
    ..This mAb and the protein recognized by it serve as an excellent marker for neurons in the central and peripheral nervous systems in both the embryo and adult, and the protein may be important in the determination of neuronal phenotype...
  48. pmc Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma
    Mara Compagno
    Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA
    Nature 459:717-21. 2009
    ..Thus, our results demonstrate that NF-kappaB activation in DLBCL is caused by genetic lesions affecting multiple genes, the loss or activation of which may promote lymphomagenesis by leading to abnormally prolonged NF-kappaB responses...
  49. ncbi Cohesins: chromosomal proteins that prevent premature separation of sister chromatids
    C Michaelis
    Research Institute of Molecular Pathology, Vienna, Austria
    Cell 91:35-45. 1997
    ..Proteins homologous to Scc1p exist in a variety of eukaryotic organisms including humans. A common cohesion apparatus might be used by all eukaryotic cells during both mitosis and meiosis...
  50. ncbi The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria
    Teresa L M Thurston
    Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, UK
    Nat Immunol 10:1215-21. 2009
    ..We conclude that human cells utilize the ubiquitin system and NDP52 to activate autophagy against bacteria attempting to colonize their cytosol...
  51. pmc An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles
    Christine M Clemson
    University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655, USA
    Mol Cell 33:717-26. 2009
    ..Collectively, results demonstrate that NEAT1 functions as an essential structural determinant of paraspeckles, providing a precedent for a ncRNA as the foundation of a nuclear domain...
  52. ncbi RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation
    Michael H Tatham
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    Nat Cell Biol 10:538-46. 2008
    ..These results demonstrate that poly-SUMO chains can act as discrete signals from mono-SUMOylation, in this case targeting a poly-SUMOylated substrate for ubiquitin-mediated proteolysis...
  53. ncbi TREX is a conserved complex coupling transcription with messenger RNA export
    Katja Strasser
    BZH, University of Heidelberg, Im Neuenheimer Feld 328, D 69120 Heidelberg, Germany
    Nature 417:304-8. 2002
    ..Our data indicate that the TREX complex has a conserved role in coupling transcription to mRNA export...
  54. ncbi Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites
    Birgit Czermin
    Adolf Butenandt Institut, University of Munich, Schillerstrasse 44, 80336 Munich, Germany
    Cell 111:185-96. 2002
    ..Histone H3 methylated in vitro by the E(Z)/ESC complex binds specifically to Polycomb protein...
  55. ncbi Histone methyltransferase activity of a Drosophila Polycomb group repressor complex
    Jurg Muller
    EMBL, Gene Expression Programme, Meyerhofstr 1, 69117 Heidelberg, Germany
    Cell 111:197-208. 2002
    ..These results identify E(Z) as a PcG protein with enzymatic activity and implicate histone methylation in PcG-mediated silencing...
  56. pmc TEAD mediates YAP-dependent gene induction and growth control
    Bin Zhao
    Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA
    Genes Dev 22:1962-71. 2008
    ..Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP...
  57. pmc Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy
    J W Miller
    Department of Molecular Genetics and Microbiology, Centers for Gene Therapy and Mammalian Genetics, University of Florida College of Medicine, Gainesville, FL 32610, USA
    EMBO J 19:4439-48. 2000
    ..We propose that DM1 disease is caused by aberrant recruitment of the EXP proteins to the DMPK transcript (CUG)(n) expansion...
  58. pmc Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein
    Andrei Kuzmichev
    Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Genes Dev 16:2893-905. 2002
    ..The presence of Su(z)12, a strong suppressor of position effect variegation, in PRC2 suggests that PRC2 may play a widespread role in heterochromatin-mediated silencing...
  59. ncbi The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
    P H Maxwell
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Nature 399:271-5. 1999
    ..Thus, constitutive HIF-1 activation may underlie the angiogenic phenotype of VHL-associated tumours. The pVHL/HIF-1 interaction provides a new focus for understanding cellular oxygen sensing...
  60. pmc Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus
    Robert R Graham
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Nat Genet 40:1059-61. 2008
    ..These results establish that variants near TNFAIP3 contribute to differential risk of SLE and RA...
  61. ncbi Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal
    Jakub Godlewski
    Dardinger Laboratory for Neuro oncology and Neurosciences, Department of Neurological Surgery, The Ohio State University Medical Center and James Comprehensive Cancer Center, Columbus, Ohio 43210
    Cancer Res 68:9125-30. 2008
    ....
  62. pmc Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity
    Diego Pasini
    European Institute of Oncology, Milan, Italy
    EMBO J 23:4061-71. 2004
    ..In conclusion, our data demonstrate an essential role of SUZ12 in regulating the activity of the PRC2/3 complexes, which are required for regulating proliferation and embryogenesis...
  63. ncbi De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling
    Ingrid E Wertz
    Department of Molecular Oncology, School of Medicine, University of California, Davis, Davis, California 95616, USA
    Nature 430:694-9. 2004
    ..We also provide an example of a protein containing separate ubiquitin ligase and DUB domains, both of which participate in mediating a distinct regulatory effect...
  64. pmc The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation
    Zichong Li
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Nucleic Acids Res 41:277-87. 2013
    ....
  65. ncbi The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
    David L Boone
    Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0451, USA
    Nat Immunol 5:1052-60. 2004
    ..The critical function of this deubiquitinating enzyme in the restriction of TLR signals emphasizes the importance of the regulation of ubiquitin conjugation in innate immune cells...
  66. pmc Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon
    Michael Overholtzer
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:12405-10. 2006
    ....
  67. pmc Phospho switch triggers Brd4 chromatin binding and activator recruitment for gene-specific targeting
    Shwu Yuan Wu
    Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Mol Cell 49:843-57. 2013
    ..The unmasking of bromodomains and activator recruitment, concurrently triggered by the CK2 phospho switch, provide an intriguing mechanism for gene-specific targeting by a universal epigenetic reader...
  68. pmc Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability
    Asad Umar
    Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
    J Natl Cancer Inst 96:261-8. 2004
    ....
  69. pmc A novel and universal method for microRNA RT-qPCR data normalization
    Pieter Mestdagh
    Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium
    Genome Biol 10:R64. 2009
    ..We demonstrate that the mean expression value outperforms the current normalization strategy in terms of better reduction of technical variation and more accurate appreciation of biological changes...
  70. ncbi Regulation of DNA double-strand break repair pathway choice
    Meena Shrivastav
    Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine and Cancer Center, Albuquerque, NM 87131, USA
    Cell Res 18:134-47. 2008
    ....
  71. ncbi The transcriptional coactivators p300 and CBP are histone acetyltransferases
    V V Ogryzko
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2753, USA
    Cell 87:953-9. 1996
    ..p300/CBP acetylates all four core histones in nucleosomes. These observations suggest that p300/CBP acetylates nucleosomes in concert with PCAF...
  72. pmc X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila
    Erica Larschan
    Division of Genetics, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 471:115-8. 2011
    ..Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome...
  73. pmc BET bromodomain inhibition as a therapeutic strategy to target c-Myc
    Jake E Delmore
    Department of Medical Oncology, Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA
    Cell 146:904-17. 2011
    ..Efficacy of JQ1 in three murine models of multiple myeloma establishes the therapeutic rationale for BET bromodomain inhibition in this disease and other malignancies characterized by pathologic activation of c-Myc...
  74. pmc p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling
    Andrei V Budanov
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, MC0723, La Jolla, CA 92093, USA
    Cell 134:451-60. 2008
    ..Correspondingly, Sestrin2-deficient mice fail to inhibit mTOR signaling upon genotoxic challenge. Sestrin1 and Sestrin2 therefore provide an important link between genotoxic stress, p53 and the mTOR signaling pathway...
  75. pmc The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3
    Pascal Drané
    IGMBC Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch F 67400, France
    Genes Dev 24:1253-65. 2010
    ..Taken together, our data demonstrate that DAXX functions as a bona fide histone chaperone involved in the replication-independent deposition of H3.3...
  76. pmc BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair
    Amitabh V Nimonkar
    Department of Microbiology, University of California at Davis, Davis, California 95616, USA
    Genes Dev 25:350-62. 2011
    ..BLM increases the affinity of EXO1 for ends, and MRN recruits and enhances the processivity of EXO1. Our results establish two of the core machineries that initiate recombinational DNA repair in human cells...
  77. pmc Altered telomeres in tumors with ATRX and DAXX mutations
    Christopher M Heaphy
    Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
    Science 333:425. 2011
    ..ATRX mutations also correlate with abnormal telomeres in tumors of the central nervous system. These data suggest that an alternative telomere maintenance function may operate in human tumors with alterations in the ATRX or DAXX genes...
  78. ncbi UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development
    Karl Agger
    Biotech Research and Innovation Centre BRIC, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark
    Nature 449:731-4. 2007
    ..8) supports a model in which the coordinated removal of repressive marks, polycomb group displacement, and deposition of activating marks are important for the stringent regulation of transcription during cellular differentiation...
  79. ncbi How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers
    Sean D Taverna
    Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA
    Nat Struct Mol Biol 14:1025-40. 2007
    ..Changes in these interactions may have far-reaching implications for human biology and disease, notably cancer...
  80. ncbi Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells
    Li Bing Song
    State Key Laboratory of Oncology in Southern China, Sun Yat sen University Cancer Center, Guangzhou, China
    Cancer Res 66:6225-32. 2006
    ....
  81. pmc Coupling of the nucleus and cytoplasm: role of the LINC complex
    Melissa Crisp
    Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610
    J Cell Biol 172:41-53. 2006
    ..2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex)...
  82. pmc CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle
    Maximina H Yun
    Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Nature 459:460-3. 2009
    ....
  83. ncbi Posttranslational mechanisms regulate the mammalian circadian clock
    C Lee
    Department of Neurobiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Cell 107:855-67. 2001
    ..We also provide in vivo evidence that casein kinase I delta is a second clock relevant kinase...
  84. pmc Control of developmental regulators by Polycomb in human embryonic stem cells
    Tong Ihn Lee
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 125:301-13. 2006
    ..These results indicate that PRC2 occupies a special set of developmental genes in ES cells that must be repressed to maintain pluripotency and that are poised for activation during ES cell differentiation...
  85. ncbi Predicting subcellular localization of proteins based on their N-terminal amino acid sequence
    O Emanuelsson
    Stockholm Bioinformatics Center, Department of Biochemistry, Stockholm University, Stockholm, S 106 91, Sweden
    J Mol Biol 300:1005-16. 2000
    ..TargetP is available as a web-server at http://www.cbs.dtu.dk/services/TargetP/...
  86. ncbi Hypoxia--a key regulatory factor in tumour growth
    Adrian L Harris
    Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
    Nat Rev Cancer 2:38-47. 2002
    ..Many elements of the hypoxia-response pathway are therefore good candidates for therapeutic targeting...
  87. ncbi Direct regulation of TWIST by HIF-1alpha promotes metastasis
    Muh Hwa Yang
    Institutes of Biochemistry and Molecular Biology, National Yang Ming University, No 155, Sec 2, Li Niong Street, Peitou, Taipei 112, Taiwan
    Nat Cell Biol 10:295-305. 2008
    ..These results provide evidence of a key signalling pathway involving HIF-1alpha and TWIST that promotes metastasis in response to intratumoural hypoxia...
  88. ncbi XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation
    A L Shaffer
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Immunity 21:81-93. 2004
    ..Thus, XBP1 coordinates diverse changes in cellular structure and function resulting in the characteristic phenotype of professional secretory cells...
  89. ncbi NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation
    Y Yamaguchi
    Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan
    Cell 97:41-51. 1999
    ..This study reveals a molecular mechanism for DRB action and a regulatory network of positive and negative elongation factors...
  90. ncbi Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition
    Muh Hwa Yang
    Institute of Clinical Medicine, National Yang Ming University, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan
    Nat Cell Biol 12:982-92. 2010
    ..These results suggest that Twist1-induced EMT and tumour-initiating capability in cancer cells occurs through chromatin remodelling, which leads to unfavourable clinical outcomes...
  91. ncbi The SWI/SNF complex and cancer
    D Reisman
    Department of Internal Medicine, University of Michigan College of Medicine, Ann Arbor, MI 48109 0686, USA
    Oncogene 28:1653-68. 2009
    ....
  92. ncbi The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA
    Jafar Sharif
    Tohoku University Biomedical Engineering Research Organization TUBERO, 2 1 Seiryo machi, Aoba ku, Sendai 980 8575, Japan
    Nature 450:908-12. 2007
    ..The link between hemi-methylated DNA, Np95 and Dnmt1 thus establishes key steps of the mechanism for epigenetic inheritance of DNA methylation...
  93. pmc Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus
    F Damiola
    , Sciences II, , CH-1211 Geneva, Switzerland
    Genes Dev 14:2950-61. 2000
    ..Food-induced phase resetting proceeds faster in liver than in kidney, heart, or pancreas, but after 1 wk of daytime feeding, the phases of circadian gene expression are similar in all examined peripheral tissues...
  94. ncbi The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
    J Momand
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544 1014
    Cell 69:1237-45. 1992
    ..Thus, a product of the mdm-2 oncogene forms a tight complex with the p53 protein, and the mdm-2 oncogene can inhibit p53-mediated transactivation...
  95. pmc PML nuclear bodies
    Valérie Lallemand-Breitenbach
    INSERM CNRS Université Paris Diderot Institut Universitaire Hématologie U944 UMR7212, Laboratoire associé de la Ligue Nationale contre le Cancer, Hopital St Louis, 1, Av C Vellefaux 75475 Paris Cedex 10, France
    Cold Spring Harb Perspect Biol 2:a000661. 2010
    ..Functionally, PML bodies may sequester, modify or degrade partner proteins, but in many ways, PML bodies still constitute an enigma...
  96. ncbi Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation
    P Jaakkola
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
    Science 292:468-72. 2001
    ..An absolute requirement for dioxygen as a cosubstrate and iron as cofactor suggests that HIF-PH functions directly as a cellular oxygen sensor...
  97. ncbi Kinetochore recruitment of two nucleolar proteins is required for homolog segregation in meiosis I
    Kirsten P Rabitsch
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Dev Cell 4:535-48. 2003
    ..Csm1 and Pcs1 might clamp together microtubule binding sites on the same (Pcs1) or sister (Csm1) kinetochores...
  98. ncbi A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol
    Yihong Ye
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 429:841-7. 2004
    ..Derlin-1 interacts with US11, a virally encoded ER protein that specifically targets MHC class I heavy chains for export from the ER, as well as with VIMP, a novel membrane protein that recruits the p97 ATPase and its cofactor...
  99. ncbi Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis
    Hideaki Tagami
    Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Cell 116:51-61. 2004
    ..This finding provides new insights into possible mechanisms for maintenance of epigenetic information after chromatin duplication...
  100. ncbi C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation
    A C Epstein
    The Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
    Cell 107:43-54. 2001
    ....
  101. ncbi The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol
    Y Ye
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 414:652-6. 2001
    ..We propose that the Cdc48/p97-Ufd1-Npl4 complex extracts proteins from the ER membrane for cytosolic degradation...

Research Grants75

  1. Chymase-Mediated MMP Activation in Ishemia Reperfusion Injury
    LOUIS JOSEPH DELL'ITALIA; Fiscal Year: 2013
    ....
  2. Regulation of HSV-1 Gene Expression and Replication by Nuclear Hormone Receptors
    SHAOCHUNG VICTOR HSIA; Fiscal Year: 2013
    ..The long-term goal is to identify the regulatory mechanisms to assist in the development of novel therapeutic protocols for better treatments. ..
  3. Phosphorylation of FGF23 coordinates crosstalk between the skeleton and kidney
    VINCENT SCOTT TAGLIABRACCI; Fiscal Year: 2013
    ..The proteins known as "casein kinases" are in fact cytosolic and nuclear proteins and do not mediate physiological phosphorylation of casein because they are spatially restricted from the ..
  4. Regulation of LPS-mediated HMGB1 Release by Poly (ADP-ribose) Polymerase-1
    RAJESH K ANEJA; Fiscal Year: 2013
    ..Additional studies will be performed to determine the therapeutic window for use of PARP-1 inhibitors in murine sepsis. ..
  5. Link of beta cell proliferation and type 2 diabetes to epigenetic regulation
    Xianxin Hua; Fiscal Year: 2013
    ..These studies will likely pave the way to develop the next generation of new drugs to treat this widespread disease. ..
  6. MOLECULAR BIOLOGY OF HEMORRHAGIC SHOCK
    Timothy R Billiar; Fiscal Year: 2013
    ..Based on our progress thus far, we are fully confident that our approach will continue to lead to productive collaboration and effective testing of a novel and important hypotheses. ..
  7. Regulation of insulator function and globin gene expression by USF and associated
    Suming Huang; Fiscal Year: 2013
    ..In this proposal, we will investigate the epigenetic mechanisms by which nuclear proteins USF1/2 regulate globin gene expression and chromatin barrier function in the globin loci...
  8. Theranostic Nanomedicine for Breast Cancer Prevention and Image-Guided Therapy
    Prakash R Rai; Fiscal Year: 2011
    ..Nanotechnology has made major contributions to BrCa therapy. We propose an innovative nanotechnology-based approach for BrCa prevention and treatment that could significantly impact patient care. ..
  9. REGULATION OF NUCLEAR ENVELOPE ASSEMBLY AND DISASSEMBLY
    Katherine L Wilson; Fiscal Year: 2012
    ..Our previous studies of BAF, the shared partner for emerin and all other LEM-domain nuclear proteins, demonstrated essential and broad-ranging roles in chromatin structure, mitotic chromosome segregation, ..
  10. Developing a New Antioxidant Activator to Intervene in Lung Inflammatory Diseases
    JOHN WILLIMANN; Fiscal Year: 2009
    ..The goal of this project is to isolate and test the effectiveness of an agent found in an essential oil that has been demonstrated to activate broad synthesis of protective antioxidants in the lung. ..
  11. Theranostic Nanomedicine for Breast Cancer Prevention and Image-Guided Therapy
    Prakash R Rai; Fiscal Year: 2013
    ..This provides the potential for rapid screening to establish individualized patient-specific molecular targets and forms the basis for designing personalized prevention and treatments. ..
  12. Link of beta cell proliferation and type 2 diabetes to epigenetic regulation.
    Xianxin Hua; Fiscal Year: 2010
    ..The proposed studies may pave the way to developing novel and menin pathway-based strategies to treat T2D. ..
  13. Role of Protein Acetylation in Ncx1 Expression
    Donald R Menick; Fiscal Year: 2012
    ..In recent years, studies have shown that acetylation and deacetylation of cystolic and nuclear proteins play an important regulatory role in mediating the rapid and long-term changes in gene expression in response ..
  14. microRNA analysis of neurons generated from patient-specific iPSCs
    Herbert M Lachman; Fiscal Year: 2013
    ..Such common pathways would be ideal targets for medication development that could be effective in a large subgroup of patients. ..
  15. Function of the Zinc Finger Protein ZPR1 in neurodegeneration
    LAXMAN DASS GANGWANI; Fiscal Year: 2013
    ..We will examine the role of cytoplasmic and nuclear proteins that interact with ZPR1 and may mediate nuclear export/import of ZPR1 and SMN...
  16. Small Molecule Probes for TAR DNA Binding Protein 43_TDP-43
    Allen B Reitz; Fiscal Year: 2012
    ....
  17. METABOLIC EFFECTS OF THYROID HORMONE
    Herbert Samuels; Fiscal Year: 2009
    ..These studies should provide a more comprehensive picture of how these factors modulate NR function and other important biological processes in cells. ..
  18. Endogenous regulators of inflammation in liver ischemia/reperfusion
    Allan Tsung; Fiscal Year: 2013
    ..g. myocardial infarction and cerebral ischemia). ..
  19. Coordinate Regulation Of Nuclear DGK-theta and PLD
    DANIEL RABEN; Fiscal Year: 2009
    ..We believe that an understanding of nuclear lipid signaling is key to our ability to intervene in events such as wound repair and tissue remodeling. ..
  20. Trophic factors and regulation of hippocampal neuroplasticity in the human brain
    Maura Boldrini; Fiscal Year: 2012
    ..These results have implications for understanding the possibility to use trophic factors as ADT in MDD. ..
  21. Degradation of Short Lived Regulatory Protein in Yeast
    MARK W HOCHSTRASSER; Fiscal Year: 2013
    ....
  22. Function of MTG16/ETO2 in acute leukemia
    SCOTT HIEBERT; Fiscal Year: 2010
    ..MTG family members are nuclear proteins that appear to function as transcriptional co-repressors that link regulatory DNA binding proteins to histone ..
  23. Regulation of Steroidogenic Genes by Trophic Hormones
    Marion B Sewer; Fiscal Year: 2013
    ..as PKA and PKC direct temporally distinct and reversible post-translational modifications (PTMs) of several nuclear proteins, including SF-1...
  24. Nuclear cofactors in hormone signaling
    Hongwu Chen; Fiscal Year: 2012
    ..Understanding the process will provide novel insights to the underlying molecular mechanisms of steroid receptor function in female reproduction and breast cancers as well as other endocrine disorders. ..
  25. TOX, a Novel Regulator of Thymocyte Selection
    JONATHAN G KAYE; Fiscal Year: 2013
    ..This research program is directed at understanding the function of a small family of nuclear proteins, highly conserved in rodents and humans, in regulating this process...
  26. O-GlcNAc Modification in Metabolic Homeostasis
    Xiaoyong Yang; Fiscal Year: 2013
    ..through the hexosamine biosynthetic pathway leads to the posttranslational modification of cytoplasmic and nuclear proteins by O-linked 2-N-acetylglucosamine (O-GlcNAc)...
  27. Cancer cell signaling through lipids complexed to proteins
    RAYMOND DANIEL BLIND; Fiscal Year: 2013
    ..on a manuscript currently in revision at Science, we hypothesize that PIP lipids bound to NR5As (and other nuclear proteins) are directly remodeled by the PI3- kinase inositol polyphosphate multikinase (IPMK) and the PTEN lipid ..
  28. Epigenetic Regulation in Self-Renewing and Differentiating Male Germ Cells
    CHRISTOPHER JESS PAYNE; Fiscal Year: 2012
    ..This project is now poised to enter the ROO phase, extending the progress made during the K99 phase and achieving the major aspects of both specific aims. ..
  29. PROTEIN SEQUENCING BY TANDEM MASS SPECTROMETRY
    Donald F Hunt; Fiscal Year: 2013
    ..will also characterize the substrate motif for a protein n-terminal methyltransferase, NRMT, identify human nuclear proteins that are trimethylated on the n-terminus, and identify and characterize the demethylase that removes this ..
  30. Progranulin, TDP-43 and Cell Death
    Leonard Petrucelli; Fiscal Year: 2013
    ..Our hypothesis is that loss of functional PGRN leads to loss of functional TDP-43, which leads to cell death. ..
  31. TRANSCRIPTIONAL REGULATION DURING SPERMIOGENESIS
    Prabhakara P Reddi; Fiscal Year: 2010
    ..The study is relevant to male reproductive health as leads can be applied to develop novel male contraceptives. The SP-10 promoter will be useful for gene therapy to treat infertility or germ cell defects. ..
  32. Genetic Analysis of T Cell Leukemogenesis
    Stephen J Brandt; Fiscal Year: 2013
    ..This or a related complex mediates the oncogenic actions of these nuclear proteins by activating and repressing the transcription of specific sets of target genes...
  33. Regulation of Aromatase Expression in the Corpus Luteum
    CARLOS OSCAR STOCCO; Fiscal Year: 2012
    ..that aromatase expression in corpora lutea of pregnant rats correlates with changes in the binding of luteal nuclear proteins to an activation protein 3 response element (AP3-RE) found in the proximal promoter...
  34. Duplin: A Novel A-Kinase Anchoring Protein
    MAUREEN E O apos DONNELL; Fiscal Year: 2010
    ..This study will test the hypothesis that the nuclear protein duplin/Chd8 mediates PKA-dependent regulation of STATS, exploring a potential mechanism by which STATS regulation could go awry in the failing heart. ..
  35. Adenosine Receptors and Ethanol Withdrawal
    TRACY RENEE BUTLER; Fiscal Year: 2010
    ....
  36. Spatiotemporal Regulation of Intestinal Gene Expression
    Eric Sibley; Fiscal Year: 2013
    ..Preliminary studies have shown that DNA sequences in the region of lactase gene polymorphisms can bind nuclear proteins and enhance lactase promoter activity...
  37. Molecular Activities of Angiogenin in the Nucleus
    KIMBERLY ANNE DICKSON; Fiscal Year: 2012
    ..is to understand the specific molecular activities of human angiogenin (ANG), including its interactions with nuclear proteins, DNA, and RNA...
  38. Beta Cell Regeneration by an Epigenetic Pathway
    Xianxin Hua; Fiscal Year: 2013
    ..These studies will likely unravel novel mechanisms of beta cell regeneration, paving the way to develop a novel menin pathway-based therapy to treat diabetes. ..
  39. The role of HMGB-1 and innate immunity in promoting angiogenesis after ischemia
    Ulka Sachdev; Fiscal Year: 2013
    ..The second aim is to determine the function of HMGB-1 and autophagy in skeletal muscle angiogenesis in vivo. The third aim is to identify a role for the TLRs in mediating the angiogenic actions of HMGB1. ..
  40. Nuclear Export of Retroviral RNPs: Cytoplasmic fates determined in the nucleus
    REBECCA J KADDIS; Fiscal Year: 2013
    ..To address this question, we used RNA affinity capture to identify nuclear proteins that bound to the retroviral 5'untranslated region (UTR)...
  41. Post-transcriptional Gene Regulation by EBV SM Protein
    Sankar Swaminathan; Fiscal Year: 2013
    ..This proposal is to study how EBV manipulates the infected cell to avoid the immune response (host defenses) and enhance its own replication. ..
  42. Function of KLF4-expressing stem cells in mouse cutaneous wound healing
    Walden Ai; Fiscal Year: 2013
    ....
  43. Nucleocytoplasmic Transport in Skeletal Muscle
    Grace K Pavlath; Fiscal Year: 2013
    ..The subcellular localization of these nuclear proteins must be tightly controlled because altered nuclear import or export could result in aberrant muscle mass and ..
  44. Investigation of an unconventional co-repressor complex
    Yang Shi; Fiscal Year: 2012
    ..Findings will provide new insights into mechanisms that control these processes and may help future development of small molecules that modulate metabolism, aging and oncogenesis. ..
  45. Computational Resources for the Compilation and Distribution of Transcription Fac
    Wyeth W Wasserman; Fiscal Year: 2012
    ..Gene regulation is performed in part by nuclear proteins called transcription factors, many of which recognize specific DNA sequences within and surrounding genes...
  46. The Nucleocytoskeleton in Progeria and Aging
    Howard J Worman; Fiscal Year: 2013
    ....
  47. Men1 Control of Endocrine Cell Growth and Differentiation
    Seung K Kim; Fiscal Year: 2010
    ..Menin associates with other nuclear proteins and chromatin to promote specific covalent histone modifications that can activate or repress target gene ..
  48. The regulation of mRNA export by microRNAs
    Melanie L Yarbrough; Fiscal Year: 2011
    ..These events are facilitated by the association of nuclear proteins such as mRNA export factors with mRNA, which ensure that processed transcripts interact with and translocate ..
  49. Mechanisms regulating PKGI proteolysis and modulation of pulmonary SMC phenotype
    Jesse D Roberts; Fiscal Year: 2013
    ..Emerging evidence suggests that cGMP-stimulated PKGI nuclear localization and phosphorylation of nuclear proteins and transcription factors, such as CREB and ATF-1, regulate SMC phenotype...
  50. REGULATION OF IRON METABOLISM GENES IN EUKARYOTES
    William E Walden; Fiscal Year: 2010
    ..Each of the cytosolic CIA factors is essential for FeS cluster assembly in cytoplasmic and nuclear proteins, and for yeast viability...
  51. Role of genome organizer Satb1 in Shh-dependent proliferation and tumorigenesis
    FRANCES YUN CHENG; Fiscal Year: 2013
    ..Understanding how genes are abnormally turned on or off in these cells will improve our knowledge of this tumor and ultimately provide insight into more effective and targeted treatments. ..
  52. Connexin acetylation: Impact on gap junction function and HDAC inhibitor respons
    JEANNETTE CHLOE BULINSKI; Fiscal Year: 2010
    ..Acetylation of non-nuclear proteins has not been extensively analyzed...
  53. Mechanisms of Epstein-Barr Virus Persistence
    Jeffery T Sample; Fiscal Year: 2013
    ..during the early establishment phase of persistent infection. Central to this phase are a family of six EBV nuclear proteins (EBNAs) that are expressed from one of two common promoters (Wp and Cp)...
  54. Mechanisms of glucosamine ischemic cardioprotection
    John C Chatham; Fiscal Year: 2010
    ..Recently, increased levels of N-acetylglucosamine (0-GlcNAc) on cytoplasmic and nuclear proteins have been linked to improved cell survival in response to stress...
  55. Genome-wide protein-DNA interactions responding to chronic opioid treatment
    Yulong Chen; Fiscal Year: 2012
    ..Since binding of nuclear proteins to the regulatory regions of a gene is one of the fundamental steps to regulate transcription of the gene, ..
  56. Translational Control by Osmotically Active Solutes
    Maria Hatzoglou; Fiscal Year: 2013
    ..Regulation of the subcellular localization of nuclear proteins by extracellular signaling is an understudied and emerging area of research...
  57. Identifying mechanisms of liver stem cell proliferation and differentiation
    CARL BARTH ROUNTREE; Fiscal Year: 2010
    ..We will downregulate HNF4a using siRNA to block differentiation in-vitro. We will isolate nuclear proteins from proliferating oval cells and control populations to define transcription factor profile important to ..
  58. NuMA function in nonmalignant and malignant breast cells
    SOPHIE A LELIEVRE; Fiscal Year: 2012
    ..Thus, it is time to emphasize the role of structural nuclear proteins in gene transcription in order to get a complete picture of gene expression control.
  59. Mechanism and Function of Chromatin Positional Dynamics in Interphase
    Alexandra Zidovska; Fiscal Year: 2013
    ..behavior of chromatin (DNA and associated proteins) has traditionally been studied by live cell microscopy of nuclear proteins, single genes, subchromosomal foci and chromosomal territories [Marshall et al. 1997;Belmont et al...
  60. In Vivo Model of Epstein-Barr Virus Latency
    RICHARD M LONGNECKER; Fiscal Year: 2012
    ..Six are nuclear proteins (EBNAs) and three are the integral membrane proteins, LMP1, LMP2A, and LMP2B...
  61. Ubiquitin-dependent proteolysis: Specificity & Mechanism
    Keith D Wilkinson; Fiscal Year: 2010
    ..Second, a modern systems biology approach takes advantage of our synthesis of polyubiquitin chain analogs to identify ubiquitin-binding proteins with specificity for different ubiquitin domains and different architectures (Aim 3). ..
  62. Self-Organization of the Human Genome
    STEVEN TODD KOSAK; Fiscal Year: 2011
    ..dynamics by attempting to create de novo a subnuclear body of unique function by non-hierarchical assembly of nuclear proteins. Combined, these approaches will yield new insight into the effect self-organization has on the human genome ..
  63. CARDIAC MUSCLE CELL DEVELOPMENT AND NUCLEAR PROTEINS
    JASWANT BHORJEE; Fiscal Year: 1990
    ..William Claycomb...
  64. MOLECULAR MECHANISMS OF NUCLEAR PROTEIN IMPORT
    Mary Moore; Fiscal Year: 1999
    ..A variety of techniques will be used to address this question including immunolocalization and immunoprecipitations and the tracking of labelled import factors during import. ..
  65. Functional Analysis of an hnRNP C-Like Protein, p542
    JAMES MCAFEE; Fiscal Year: 2004
    ..have been identified in the heterogeneous nuclear ribonucleoproteins C1 and C2 (hnRNP C), two very abundant nuclear proteins associated with pre-mRNA processing, regulation of mRNA stability, and translation...
  66. ANTIBODIES TO NUCLEAR PROTEINS IN CERVICAL CANCER
    EDWARD FEY; Fiscal Year: 1992
    Antibodies to nuclear proteins in cervical cancer. The Pap smear, an important clinical screen for uterine cervical cancer, has limited prognostic value for individual patients...
  67. NUCLEOCYTOPLASMIC TRAFFICKING
    David Goldfarb; Fiscal Year: 1992
    ..natural substrates such as genetically engineered fusion proteins containing signal sequences, and endogenous nuclear proteins. Whether or not any of these substrates share steps along the cell's trafficking pathway will be determined ..
  68. Role of Protein (S14)in Normal and Neoplastic Mammary
    WILLIAM KINLAW; Fiscal Year: 2005
    ..These studies will provide a comprehensive view of the role of this novel nuclear protein in both normal mammary physiology and in breast cancer, and are likely to reveal a new class of therapeutic targets. ..
  69. NUCLEOPROTEINS IN MAMMALIAN SPERMATOGENESIS
    Marvin Meistrich; Fiscal Year: 2006
    ..spermiogenesis) is characterized the displacement of histones, at which time two major basic transition nuclear proteins (TPI and TP2) become predominant in the nucleus. These are in turn replaced by protamines...
  70. CYTOPLASMIC FACTORS IN NUCLEAR PROTEIN IMPORT
    Stephen Adam; Fiscal Year: 2000
    The long term goal of this application is to understand the mechanisms by which cells localize nuclear proteins via a specific transport pathway...
  71. NUCLEAR PROTEINS AND AUTOIMMUNITY
    SALLIE HOCH; Fiscal Year: 1992
    ..This research is directed toward the characterization of the nuclear proteins that serve as indicators of various rheumatic diseases, including systemic lupus erythematosus (SLE) and ..
  72. MECHANISMS OF NUCLEAR PROTEIN ACCUMULATION
    PHILIP PAINE; Fiscal Year: 1993
    ....
  73. VITAMIN D MEDIATED GENE REGULATION IN B LYMPHOCYTES
    John Morgan; Fiscal Year: 2000
    ..These studies will help to delineate mechanisms governing 1,25D-mediated gene regulation in normal human B lymphocytes, and may allow for further characterization of vitamin D as a mediator of the immune response. ..
  74. SPECIFIC INHIBITION OF K-RAS EXPRESSION IN LUNG CANCER
    CHARLES MAYFIELD; Fiscal Year: 1999
    ..These studies will provide critical information on the potential for antigene therapy in humans. ..
  75. Factor X: A Cardiac-Specific Transcriptional Regulator
    Charles Ordahl; Fiscal Year: 2006
    ..for an abundant nuclear enzyme that catalyzes the formation of poly ADP-ribose chains on itself and other nuclear proteins. PARP I is known to be a multi-functional enzyme but only one of its roles has been analyzed in detail, ..